The immune response has been shown to play a decisive role in the outcome of experimentally produced viral infections of the rodent central nervous system (CNS). Conventionally, primary CNS infections produced by cytocidal arboviruses, unless checked and eliminated by a specific anti- viral immune response, usually result in progressive tissue destruction and, eventually, lead to the death of the host. In contrast, infections produced in the murine host by members of the arenavirus group may lead, under appropriate conditions, to either a non-cytopathic, persistent CNS infection or an acutely fatal CNS disease which is mediated by an anti- viral immune response. These contrasting roles of virus-specific immune induction are strikingly illustrated through the use of immunosuppression which can either potentiate, or protect against, disease. The major objectives of this project are: (1) to study the contrasting effects of immunosuppression on the pathogenesis of experimental West Nile and lymphocytic choriomeningitis virus infections of the rodent; (2) to use the immunosuppressed virus-infected animal as a recipient of adoptively transferred lymphoid cells or serum obtained from syngeneic, virus-immune donors in an attempt to assess the relative contributions of the cellular and humoral immune responses to aborting the infectious process or eliciting immunopathology and CNS disease and, (3) to employ recently developed methods for correlative measurements, in viiro, of virus-specific immune reactivity of lymphoid cells from normal, immunosuppressed and immunologically reconstituted animals during the course of viral infections.